Human IFN had an antiviral activity in bovine embryonic kidney cells that resulted in the release of VSV particles with decreased infectivity. Examination of the proteins of VSV releases from bovine cells following IFN treatment showed a selective inhibition in the glycoprotein. Electron microscopic studies also revealed that virions released from IFN-treated cells lacked the characteristic surface projections. Treatment of mouse L or human foreskin fibroblast cells with IFN results in a significant inhibition of the biosynthesis of N-acetyl glucosaminyl-lipids that serve as precursors for the biosynthesis of glycoproteins. In IFN-treated membrane preparations from uninfected L-cells, the ratio of N-acetylglucosamine (GlcNAc)-to N,N'-diacetylchitobiose (GlcNAc)2-lipids is increased, however, in membranes prepared from L-cells infected with VSV, a reversal in the ratio of GlcCAc to (GlcNAc)2 is observed. This may be related to membrane alteration in the cells since these cells have markedly elevated levels of membrane bound glycosyltransferase activities upon VSV infection.